+ Translate
+ Most Popular
The pigeon tick (Argas reflexus): its biology, ecology, and epidemiological aspects
Prevalence of hemoglobin abnormalities in Kebili (Tunisian South)
Lipogranuloma: a preventable complication of dacryocystorhinostomy
Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency
Bees from the Belgian Congo. The acraensis group of Anthophora
Placing gingival retraction cord
Total serum IgE, allergy skin testing, and the radioallergosorbent test for the diagnosis of allergy in asthmatic children
Acariens plumicoles Analgesoidea parasites des oiseaux du Maroc
Injuries of terminal phalanges of the fingers in children
Biology of flowering and nectar production in pear (Pyrus communis)
Das Reliktvorkommen der Aspisviper (Vipera aspis L.) im Schwarzwald
Hydrological modelling of drained blanket peatland
Pathologic morphology and clinical significance of the anomalous origin of the left circumflex coronary artery from the right coronary artery. General review and autopsy analysis of 30 cases
Cyto genetic analyses of lymphocyte cultures after exposure to calcium cyclamate
Axelrodia riesei, a new characoid fish from Upper Rio Meta in Colombia With remarks concerning the genus Axelrodia and description of a similar, sympatric, Hyphessobrycon-species
Favorable evolution of a case of tuberculosis of pancreas under antibiotic action
RIFM fragrance ingredient safety assessment, Valencene, CAS Registry Number 4630-07-3
Parenteral microemulsions: an overview
Temperate pasture: management for grazing and conservation
Evaluation of a new coprocessed compound based on lactose and maize starch for tablet formulation
Thermal expansion and cracking of three confined water-saturated igneous rocks to 800C
Revision of the genera of the tribe Stigmoderini (Coleoptera: Buprestidae) a discussion of phylogenetic relationships
Anal tuberculosis. Report of a case
Gastric tuberculosis in the past and present
Adaptive responses of the cardiovascular system to prolonged spaceflight conditions: assessment with Holter monitoring

A select set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat kappa-opioid receptor in human embryonic kidney 293 cells

A select set of opioid ligands induce up-regulation by promoting the maturation and stability of the rat kappa-opioid receptor in human embryonic kidney 293 cells

Journal of Pharmacology and Experimental Therapeutics 323(2): 614-625

ISSN/ISBN: 0022-3565

PMID: 17720886

DOI: 10.1124/jpet.107.125500

Ligand-induced regulation of the rat (K)-opioid receptor ( rKOR) was investigated in human embryonic kidney 293 cells stably expressing the FLAG-tagged rKOR. Incubation of rKOR cells with naltrexone for 24 h increased the B-max > 3- fold, with no change in the affinity of [H-3] diprenorphine. Two immunoreactive receptor species were present in cell lysates: naltrexone treatment caused a > 3-fold increase in the 52-kDa species while decreasing the level of the 42-kDa species. Dynorphin(1-13), U69,593 [(5 alpha,7 alpha,8 beta)-( + )N- methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro[4,5]dec-8-yl)benzeneacetamide], or salvinorin A [2S,4aR,6aR,7R,9S,10aS, 10bR)-9-(acetyloxy)-2-(3-furanyl) dodecahydro-6a, 10b-dimethyl-4,10- dioxo-2H-naphtho[2,1c] pyran-7-carboxylic acid methyl ester] treatment did not alter the level of immunoreactive rKOR protein, whereas etorphine, cyclazocine, naloxone, and naloxone methiodide increased the 52-kDa and decreased the 42-kDa rKOR bands. Receptor up-regulation was associated with an increase in the number of cell surface receptors and a 2-fold increase in the E-max for guanosine 5'-O( 3-[S-35]thio)triphosphate binding. Glycosidase digestion indicated that the 52- and 42-kDa receptors contained complex and high-mannose N-glycans, respectively, Pulse-chase analysis and glycosidase digestion sensitivities suggested that the 42-kDa rKOR species was a precursor of the 52-kDa species. Naltrexone did not alter rKOR mRNA levels or translational efficiency, and rKOR up-regulation was not inhibited by cycloheximide. Brefeldin A caused accumulation of intracellular rKOR intermediates, and coincubation with naltrexone increased the levels of the brefeldin-induced species significantly. These results suggest that select opioid ligands upregulate rKOR by enhancing the rate of receptor folding and maturation and by protecting the receptor from degradation, resulting in an increase in the number of rKOR binding sites, immunoreactive protein, and functional receptors.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 029782886

Download citation: RISBibTeXText

Related references

Opioid regulation of the mouse delta-opioid receptor expressed in human embryonic kidney 293 cells. Molecular Pharmacology 52(2): 272-281, 1997

Inhibition of agonist-induced down-regulation of the delta-opioid receptor with a proteasome inhibitor attenuates opioid tolerance in human embryonic kidney 293 cells. Journal of Pharmacology and Experimental Therapeutics 320(3): 1186-1194, 2007

Differential pharmacological actions of methadone and buprenorphine in human embryonic kidney 293 cells coexpressing human μ-opioid and opioid receptor-like 1 receptors. Neurochemical Research 36(11): 2008-2021, 2011

Functional interaction among opioid receptor types: up-regulation of mu- and delta-opioid receptor functions after repeated stimulation of kappa-opioid receptors. Neuropharmacology 46(4): 531-540, 2004

Up-regulation of RGS4 mRNA by opioid receptor agonists in PC12 cells expressing cloned mu- or kappa-opioid receptors. European Journal of Pharmacology 433(1): 29-36, 2001

An approach to the rational design of opioid receptor ligands Non-narcotic kappa-opioid receptor ligand KT-95 free from euphoria and/or dysphoria. Current Medicinal Chemistry - Central Nervous System Agents 1(1): 1-25, 2001

Regulation of human B lymphocyte activation by opioid peptide hormones. Inhibition of IgG production by opioid receptor class (mu-, kappa-, and delta-) selective agonists. Journal of Neuroimmunology 65(1): 21-30, 1996

A truncated kappa opioid receptor shows a loss of affinity for highly kappa-selective, but not non-selective, opioid ligands. Society for Neuroscience Abstracts 24(1-2): 1094, 1998

Design and synthesis of kappa-delta opioid bivalent ligands as probes to study opioid receptor dimerization. Abstracts of Papers American Chemical Society 224(1-2): MEDI 242, 2002

Synthesis and opioid receptor binding affinities of 2-substituted and 3-aminomorphinans: ligands for mu, kappa, and delta opioid receptors. Journal of Medicinal Chemistry 53(1): 402-418, 2010

Interaction of bivalent ligand KDN21 with heterodimeric delta-kappa opioid receptors in human embryonic kidney 293 cells. Molecular Pharmacology 68(4): 1079-1086, 2005

Differential efficacies of kappa agonists to induce homologous desensitization of human kappa opioid receptor. Neuroscience Letters 240(1): 25-28, 1998

Characteristics of diprenophrine binding to kappa opioid receptors in human cortex Kappa opioid receptor heterogeneity. Regulatory Peptides 54(1): 149-150, 1994

Heterologous mu-opioid receptor adaptation by repeated stimulation of kappa-opioid receptor: up-regulation of G-protein activation and antinociception. Journal of Neurochemistry 85(5): 1171-1179, 2003

Studies on drug dependence Short-term up-regulation of muu-opioid receptor functions after repeated administration of the kappa-opioid receptor agonist in the thalamus of rodents. Journal of Pharmacological Sciences 94(Suppl. 1): 227P, 2004